Sodium Carbonate → HCID 178476632, compound

Participants

Reaction Steps

A mixture of N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-N-[6-(trifluoromethyl)benzo[d]isoxazol-3-yl]amine (0.062 g, 0.000153 mol), trans-3-iodo-1-[4-(4-methylpiperazino)-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.065 g, 0.000146 mol), tetrakis-(triphenylphosphine)palladium (0.010 g, 0.0000087 mol) and sodium carbonate (0.039 g, 0.000365 mol) was heated in a mixture of ethylene glycol dimethyl ether (4 mL) and water (2 mL) at 80° C. for 16 hours under an atmosphere of nitrogen. The mixture was allowed to cool to ambient temperature and solvents were removed under the reduced pressure. The residue was purified by preparative HPLC (Hypersil C18, 8 μm, 25 cm; 10-70% acetonitrile-0.1M ammonium acetate over 30 min, 21 mL/min) to yield trans-N3-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)-6-(trifluoromethyl)benzo[d]isoxazol-3-amine acetate (0.026 g, 0.0000398 mol) as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 10.05 (s, 1H), 8.44 (d, 1H), 8.23 (s, 1H), 8.16 (s, 1H), 7.88 (d, 2H), 7.79 (d, 1H), 7.69 (d, 2H), 4.67 (m, 1H), 2.6-2.2 (br, 9H), 2.13 (s, 3H), 2.05 (m, 6H), 1.91 (s, 3H), 1.46 (m, 2H); RP-HPLC (Delta Pak C18, 5 μm, 300 A, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 20 min, 1 mL/min) Rt 16.18 min. MS: MH+ 592.

Provenance & Evidence